SM_253b: Platelet Function and Formation

Question 1

This is a ____

Answer 1

Megakaryocyte

Question 2

Describe megakaryocyte and platelet development

Answer 2

Megakaryocyte and platelet development

1. CFU-GEMM
2. BFU-Meg
3. CFU-Meg
4. Promegakaryoblast
5. Megakaryoblast
6. Promegakaryocyte
7. Megakaryocyte

Question 3

Describe proplatelet cytoskeletal mechanics

Answer 3

Proplatelet cytoskeletal mechanics

1. Transcriptional amplification
2. Organelle synthesis
3. Platelet-specific protein amplification
4. Microtubules move to cortex
5. Proplatelet elaboration
6. Microtubule sliding and tracking of granules / organelles to nascent platelets
7. End amplification via branching
8. Proplatelet release
9. Platelet release
10. Nuclear material shed (apoptosis)

Question 4

Platelets are formed from ___

Answer 4

Platelets are formed from megakaryocytes in the bone marrow

• Each megakaryocyte gives rise to mutlple platelets

Question 5

___ is the principle regulator of thrombopoiesis

Answer 5

Thrombopoietin is the principle regulator of thrombopoiesis

Question 6

Describe platelet lifespan and fate

Answer 6

Platelet lifespan and fate

• 19⁹ megakaryocytes
• Turnover: 10-14% per day
• 1.25 x 10¹² circulating platelets

Question 7

Describe causes of thrombocytopenia due to impaired platelet function

Answer 7

Thrombocytopenia due to impaired platelet function

• Congenital: MYH-9 related, Mediterranean / familial, Wiskott-Aldrich
• Acquired: HIV infection, chemo and radiation therapy, nutritional and alcohol induced, acute or chronic leukemia / stem cell transplant, bone marrow failure (aplastic anemia and others)

Question 8

When platelet production decreases turnover ____ and number of circulating platelets ____

Answer 8

When platelet production decreases turnover decreases and number of circulating platelets decreases

Question 9

___ causes impaired platelet production

Answer 9

Wiskott-Aldrich syndrome causes impaired platelet production

Question 10

As platelet count increases, platelet survival ____ and fraction removed ____

Answer 10

As platelet count increases, platelet survival increases and fraction removed increases

Question 11

Describe intrinsic pathway of apoptosis

Answer 11

Intrinsic pathway of apoptosis

1. Lack of survival signals, irradiation / DNA damage
2. Activation of sensors (BH3-only sensors)
3. Antagonist of Bcl-2
4. Activation of Bax/Bak channel
5. Leakage of cytochrome c and other proteins
6. Activations of caspases
7. Apoptosis

Question 12

Describe causes of thrombocytopenia due to increased platelet clearance

Answer 12

Thrombocytopenia due to increased platelet clearance

• Bleeding
• Thrombosis
• Consumptive coagulopathy
• Sepsis
• Thrombotic thrombocytopenia purpura
• Immune thrombocytopenia purpura
• Drugs / heparin-induced thrombocytopenia
• Splenomegaly: splenic sequestration

Question 13

In immune thrombocytopenia, turnover ____ and number of circulating platelets ____

Answer 13

In immune thrombocytopenia, turnover increases and number of circulating platelets decreases

Question 14

Platelet life-span is ___ and regulated by ___

Answer 14

Platelet life-span is 8-10 days and regulated by intrinsic apoptosis pathway

Question 15

Platelets help maintain ____

Answer 15

Platelets help maintain endothelium

Question 17

Describe platelet function

Answer 17

Platelet function

• Adhere to subendothelium of a damaged blood vessel
• Recruit additional platelets
• Provide a surface for blood coagulation to occur
• Clot maturation
• Provide growth factors for wound repair
• Endothelial maintenance function
• Adjuvant immune function

Question 18

Describe stages of platelet activation and thrombus formation

Answer 18

Stages of platelet activation and thrombus formation

1. Unstable adhesion
2. Aggregation
3. Thrombin generation
4. Contraction / clotting

Question 19

Platelet receptor-ligand interactions are involved in ____ and ____

Answer 19

Platelet receptor-ligand interactions are involved in translocation and stable adhesion

Question 20

Platelet adhesion involves ____, ____, ____, ____, and ____

Answer 20

Platelet adhesion involves GPIa/IIa, GPIX-V, GPIb, GPVI, and vWF

Question 21

Platelet aggregation involves ____, ____, ____, ____, ____, ____, and ____

Answer 21

Platelet aggregation involves GPIb, GPIX-V, GPIIb/IIIa, vWF, p-selectin, and fibrinogen

Question 22

Describe contents of delta (dense) granules

Answer 22

Delta (dense) granules

• ADP
• ATP
• Serotonin
• Pyrophosphate
• Calcium

Question 23

Describe contents of alpha granules

Answer 23

Alpha granules

• Platelet factor 4
• Beta-thromboglobulin
• Platelet derived growth factor
• Fibrinogen
• Factor V
• vWF
• HMWK

Question 24

Lysosomal vesicles contain ____

Answer 24

Lysosomal vesicles contain acid hydrolases

Question 25

Thromboxane is derived from \_\_\_

Answer 25

Thromboxane is derived from arachidonic acid

Question 26

Describe process of platelet recruitment

Answer 26

Platelet recruitment 1. Platelet granules release (ADP) 2. Thromboxane (TxA2) synthesis 3. Fibrinogen receptor (GPIIb/IIIa) activated 4. Platelets bind fibrinogen

Question 27

Membrane phospholipids are distributed by \_\_\_

Answer 27

Membrane phospholipids are distributed by phospholipid exchange proteins * Expression of PS on platelet surface provides sites for anchorage of coagulation factors * Flippases, floppases, scramblases

Question 28

Describe features of arterial thrombosis

Answer 28

Arterial thrombosis * Begins at site of turbulence or endothelial injury * Extends retrograde to flow * Platelets, tissue factor, fibrin, few RBC, WBC

Question 29

Describe features of venous thrombosis

Answer 29

Venous thrombosis * Occurs at sites of stasis * Extends in direction of flow * Contains RBCs, fibrin, and few platelets * Leukocytes, NETs, tissue factor, platelets, and microvesicles

Question 30

Summarize platelet function and hemostasis

Answer 30

Platelet function and hemostasis * Platelets play a key role in hemostasis and thrombus formation * Primary hemostasis begins with platelets adhering to the site of endothelial damage to form a platelet plug * Interaction of platelets with receptors mediates platelet adhesion and activation * Thrombin generation and coagulation cascade occurs on the surface of activated platelets

Question 31

Describe bleeding symptoms of platelet function defects

Answer 31

Bleeding symptoms of platelet function defects * Typically involves the skin or mucous membranes * Easy bruising, petechiae, epistaxis, purpuric mucocutaneous bleeding, gastrointestinal bleeding, GU bleeding, menorrhagia, excess bleeding with minor surgery or dental extraction

Question 32

\_\_\_, \_\_\_, and ___ are tests used to assess qualitative platelet defects

Answer 32

Platelet function analysis, platelet aggregation studies, and platelet flow cytometry are tests used to assess qualitative platelet defects

Question 33

Describe causes of acquired platelet function defects

Answer 33

Acquired platelet function defects * Drugs: aspirin, NSAIDs, others * Uremia: metabolic byproducts inhibit platelet function * Dysproteinemia: Waldenstrom macroglobulinemia, IgA myeloma, liver disease when fibrin degradation products interfere with platelet-fibrinogen binding * Myeloproliferative disorders * Cardiopulmonary bypass: causes platelet activation and exhaustion * Antiplatelet antibodies interfere with platelet receptors

Question 34

Bernard Soulier syndrome results from ____ defect

Answer 34

Bernard Soulier syndrome results from platelet glycoprotein GP Ib/IX (vWF receptor) defect

Question 35

Bernard Soulier syndrome presents with \_\_\_\_

Answer 35

Bernard Soulier syndrome presents with symptoms of platelet dysfunction (mucocutaneous bleeding, etc)

Question 36

Describe diagnosis of Bernard Soulier syndrome

Answer 36

Bernard Soulier syndrome diagnosis * Variable degree of thrombocytopenia * Large platelets * Abnormal platelet aggregation to ristocetin, normal aggregation with other agonists * Platelet flow cytometry with decreased surface expression of the GP Ib/IX complex

Question 37

\_\_\_\_ or ____ are used to treat Bernard Soulier syndrome

Answer 37

Platelet transfusion and desmopressin are used to treat Bernard Soulier syndrome

Question 38

Glanzmann thrombasthenia results from a ____ that leads to \_\_\_\_

Answer 38

Glanzmann thrombasthenia results from a defective GP IIb/IIIa receptor that leads to failure of platelets to bind fibrinogen and aggregate

Question 39

Glanzmann thrombasthenia presents with \_\_\_\_

Answer 39

Glanzmann thrombasthenia presents with symptoms of platelet dysfunction (mucocutaneous bleeding, etc)

Question 40

Describe diagnosis of Glanzmann thrombasthenia

Answer 40

Glanzmann thrombasthenia diagnosis * Platelet aggregation: normal aggregation with ristocetin, global abnormal aggregation with all other agonists * Platelet flow cytometry: decreased number of GP IIb/IIIa receptors

Question 41

\_\_\_ or ___ are used to treat Glanzmann thrombasthenia

Answer 41

Platelet transfusion or desmopressin are used to treat Glanzmann thrombasthenia

Question 42

Glanzmann thrombasthenia shows ____ with all agonists except \_\_\_\_

Answer 42

Glanzmann thrombasthenia shows global dysfunction with all agonists except ristocetin

Question 43

Dense granule storage pool disorder results from \_\_\_

Answer 43

Dense granule storage pool disorder results from defects in platelet dense granules

Question 44

Dense granule storage pool disorder is diagnosed via ____ and \_\_\_\_

Answer 44

Dense granule storage pool disorder is diagnosed via abnormal platelet aggregation and lack of dense granules on electron microscopy

Question 45

These are \_\_\_\_

Answer 45

Platelet granule deficiency

Question 46

This is \_\_\_

Answer 46

This is Glanzmann thrombasthenia

Question 47

Summarize congenital and acquired platelet defects

Answer 47

Congenital and acquired platelet defects * Bleeding symptoms in a patient with a normal platelet count indicate qualitative platelet defects * Qualitative platelet defects can be caused by defect in platelet receptors or granules * Symptoms of qualitative platelet defects are primarily skin and mucocutaneous bleeding